A randomised, prospective and head-to-head comparison of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 for the detection of recurrent prostate cancer in PSMA-ligand PET/CT-Protocol design and rationale.
PloS one
BACKGROUND:A number of radiopharmaceuticals are available for the detection of recurrent prostate cancer (rPC), but few comparative imaging trials have been performed comparing them. In particular, there are no prospective head-to-head comparisons of the recently introduced [18F]PSMA-1007 to the existing standard of care [68Ga]Ga-PSMA-11. The purpose of this trial is to establish the non-inferiority of the new radiopharmaceutical in terms of the rate of PET-positive findings and to obtain an intra-individual comparison of accuracy and radiopharmaceutical kinetics. METHODS:In this cross-over trial we will randomise 100 individuals to receive either first a standard-of-care PET/CT using [68Ga]Ga-PSMA-11 followed by an additional [18F]PSMA-1007 PET/CT within 2 weeks, or vice-versa. Inclusion criteria include patients 18 years and older with biochemical recurrence of prostate cancer following radical prostatectomy, defined as two consecutive prostate specific antigen (PSA) levels > 0.2 ng/ml. Detection rate at the patient-based level is the primary end-point. Each scan will be interpreted by a panel of six independent and masked readers (three for [68Ga]Ga-PSMA-11 and three for [18F]PSMA-1007) which consensus majority in cases of discrepancy. To confirm the PET-positivity rate at a patient based level, follow up at 6 months following the first scan will be performed to a composite standard of truth. Secondary endpoints shall include an intra-individual comparison of radiopharmaceutical-kinetics, per-region detection rate and positive predictive value. DISCUSSION:This is the first randomised prospective comparative imaging trial to compare the established [68Ga]Ga-PSMA-11 with [18F]PSMA-1007 and will determine whether the new radiopharmaceutical is non-inferior to the established standard-of-care in terms of patient-level detection rate. CLINICAL TRIAL REGISTRATION:Registered with and approved by the regional ethics authority #2020-02903 (submitted 09.12.2020, approval 16.12.2021) and the regulatory authority SwissMedic 2020DR2103. Registered with ClinicalTrials.gov Identifier NCT05079828 and additionally in a national language in the Swiss National Clinical Trials Portal (SNCTP).
10.1371/journal.pone.0270269
Detection Rate of PSMA PET Using Different Ligands in Men with Biochemical Recurrent Prostate Cancer Following Radical Treatment: A Systematic Review and Meta-analysis of Prospective Studies.
Academic radiology
BACKGROUND:Despite the acknowledged diagnostic detection rate of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in prostate cancer, little is known about the quality of evidence, particularly focusing on prospective studies. Most systematic reviews are based on retrospective reports. RATIONALE AND OBJECTIVES:To conduct systematic review and meta-analysis of prospective studies reporting the diagnostic detection rate of PSMA PET (computed tomography (CT) and MR) for the detection of biochemically recurrent metastatic prostate cancer. MATERIALS AND METHODS:We systematically searched PubMed, MEDLINE, Embase, and Scopus, from database until March 1, 2023 for randomized controlled trials and prospective studies using PSMA PET imaging in prostate cancer. The primary endpoint was to assess diagnostic detection rate of PSMA PET imaging in the detection of recurrent prostate cancer in men with biochemical relapse following radical treatment. We calculated the pooled overall diagnostic detection rate with 95% CI using a random-effects model and assessed the heterogeneity between the studies including risk of biases estimation. RESULTS:A total of 6800 patients from 32 articles were included in this study. The overall detection rate of PSMA PET for prostate cancer was 0.67 (95% CI, 0.63, 0.71). For histologically confirmed lymph nodes, the PPV from 13 prospective studies containing 1496 patients was 0.96 (95% CI, 0.93, 0.99). We performed a subgroup analysis of PSMA PET detection rates according to categorically grouped Prostate Specific Antigen (PSA) values of 0-0.5, 0.5-1.0, 1.0-2.0, and >2.0 ng/ml and obtained detection rates of 0.44, 0.63, 0.82, and 0.94, respectively. The detection rate of 18F PSMA was better in men with a PSA between 1 ng/ml and 2 ng/ml in comparison to 68Ga PSMA (0.91 with 95% CI 0.81-0.99 vs. 0.79 with 95% CI 0.73, 0.85). CONCLUSION:PSMA PET imaging provides a good detection rate for the metastatic recurrence of prostate cancer in men with biochemical relapse following radical treatment. The detection rate improves significantly above a serum PSA value of 1 ng/ml. The diagnostic detection rate of 18F-PSMA is best at PSA values between 1 and 2 ng/ml, in comparison to 68Ga PSMA. This conclusion is heavily biased, further research needs to focus on better methodology to minimize the risk of biases.
10.1016/j.acra.2023.08.044
Meta-analysis of F-PSMA-1007 PET/CT, F-FDG PET/CT, and Ga-PSMA PET/CT in diagnostic efficacy of prostate Cancer.
Cancer imaging : the official publication of the International Cancer Imaging Society
OBJECTIVE:To compare F-PSMA-1007 PET/CT, F-FDG PET/CT and Ga-PSMA PET/CT in the diagnostic value of prostate cancer. METHOD:The Chinese and foreign databases, such as Pubmed, Cochrane Library, Embase, CNKI, VIP, Wanfang, etc., were systematically searched within the period from the establishment of the database to June 1, 2022. Clinical studies related to the diagnosis of prostate cancer by methods such as F-PSMA-1007 PET/CT, F-FDG PET/CTCT, Ga-PSMA PET/CT, were researched. Two (2) investigators independently screened literatures, extracted data, and assessed the risk of bias when these data were included in the studies with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Review Manager5.4, Stata 14.0, and Meta-disc 1.4 software were used for meta-analysis to compare the efficacy of different methods in the diagnose of prostate cancer. RESULTS:Twenty-seven (27) studies, including 2891 subjects were included in our study. Meta-analysis results showed that the pooled sensitivities of F-PSMA-1007 PET/CT, F-FDG PET/CT, and Ga-PSMA PET/CT were 0.912 (95%CI: 0.883-0.936), 0.748 (95%CI: 0.698-0.795), and 0.916 (95%CI: 0.896-0.934), respectively; the pooled specification were 0.878 (0.844-0.907), 0.639 (95%CI: 0.589-0.687), and 0.734 (95%CI: 0.685-0.779), respectively; the positive likelihood ratios were 6.335 (95%CI: 4.288-9.357), 2.282 (95%CI: 1.497-3.477), and 3.593 (95%CI: 2.986-4.323), respectively; the negative likelihood ratios were 0.878 (95%CI: 0.844-0.907), 0.374 (95%CI: 0.280-0.499), and 0.110 (95%CI: 0.083-0.144), respectively; the diagnostic odds ratios were 65.125 (95%CI: 34.059-124.53), 7.094 (95%CI: 4.091-12.301), and 29.722 (95%CI: 20.141-43.863), respectively; the positive posterior probability was 64%, 38%, and 62%, respectively; the area under the SPOC curve was 0.95 (95%CI: 0.93-0.97), 0.81 (95%CI: 0.78-0.84), and 0.96 (95%CI: 0.92-0.98), respectively. The funnel plots indicated that there was no significant publication bias in the included literatures. CONCLUSION:The current evidences showed that F-PSMA-1007 PET/CT and Ga-PSMA PET/CT had higher diagnostic efficacy of prostate cancer compared with F-FDG PET/CT, among which Ga-PSMA PET/CT was slightly higher in the sensitivity of the diagnosis of prostate cancer, while F-PSMA-1007 PET/CT may have higher efficacy in specificity and confirmed positive rate. Due to the limitations of the quality of the included samples and literatures, the above conclusions should be further validated by expanding the sample size and improving the quality.
10.1186/s40644-023-00599-y
Histopathologically Validated Diagnostic Accuracy of PSMA-PET/CT in the Primary and Secondary Staging of Prostate Cancer and the Impact of PSMA-PET/CT on Clinical Management: A Systematic Review and Meta-analysis.
Seminars in nuclear medicine
Prostate-specific membrane antigen (PSMA) is a highly expressed protein in prostate cancer (PCa) and has become an increasingly popular target for molecular imaging in recent years. PSMA based positron-emission-tomography/computed tomography (PET/CT) is a well characterised hybrid imaging modality that combines the high sensitivity of PET with the high spatial resolution of CT imaging. The combination of these two imaging modalities provides an accurate tool for detecting and managing PCa. Several diagnostic accuracy and clinical management studies investigating the role of PSMA PET/CT in PCa have been published recently. This study aimed to perform an updated systematic review and meta-analysis to evaluate the diagnostic performance of PSMA PET/CT in localised, lymph node metastatic (LNM) and recurrent PCa patients and assess its impact on the clinical management of primary and recurrent PCa. Using Medline, Embase, PubMed and Cochrane Library databases, studies reporting the diagnostic accuracy and clinical management of PSMA PET/CT were analysed based on the PRISMA guidelines. Statistical analyses were conducted using random-effects models, and meta-regression explored observed heterogeneity. Results indicate that the sensitivity and specificity of PSMA PET/CT for localised PCa were 71.0% (95% confidence interval (CI): 58.0, 81.0) and 92.0% (95% CI: 86.0, 96.0), respectively (N = 10; n = 404 patients). Sensitivity and specificity in LNM were 57.0% (95% CI: 49.0, 64.0) and 96.0% (95% CI: 95.0, 97.0) (N = 36; n = 3,659 patients). For patients with biochemical recurrence (BCR), sensitivity was 84.0% (95% CI: 74.0, 90.0), and specificity was 97.0% (95% CI: 88.0, 99.0) (N = 9; n = 818 patients). The pooled proportion of management changes in primary (N = 16; n = 1,099 patients) and recurrent (N = 40; n = 5,398 patients) PCa was 28.0% (95% CI: 23.0, 34.0) and 54.0% (95% CI: 50.0, 58.0), respectively. In conclusion, PSMA PET/CT shows moderate sensitivity and high specificity in localised and LNM disease, while the accuracy in BCR patients was high. PSMA PET/CT also had a large impact on the clinical management of PCa patients. This is the most extensive and first systematic review to include three subgroups of PCa with histologically verified diagnostic accuracy and clinical management change reported separately in primary and recurrent disease settings.
10.1053/j.semnuclmed.2023.02.006
Ga-PSMA PET in prostate cancer: a systematic review and meta-analysis of the observer agreement.
European journal of nuclear medicine and molecular imaging
PURPOSE:The performance of Ga-PSMA PET/CT-MR has been evaluated in prostate cancer (PCa), showing significant results. However, even a technically accurate imaging procedure requires a high interobserver agreement in its interpretation to implement in patients' management. This study aims to perform a systematic review and meta-analysis on the interobserver variability in Ga-PSMA PET/CT-MR imaging in PCa patients. METHODS:We conducted a systematic review and meta-analysis on the interobserver variability, including studies: (1) providing Kappa (K) as the inter-observer agreement test or the essential data to calculate it, (2) providing the K confidence interval or the essential crude data to calculate it, (3) measuring K statistic based on the appropriate use criteria for the inter-observer agreement. RESULTS:Twelve studies, providing 1585 Ga-PSMA PET/CT-MR studies reviewed by 62 independent readers, were included. In general, the pooled inter-observer agreement was interpreted as substantial for all analyzed groups, including tumoral lesions in the prostate bed, lymphadenopathies, bone metastasis, and soft-tissue metastasis (all between 0.6 and 0.8). The regional lymphadenopathy group (0.74) obtained the highest agreement, while the lowest was for soft tissue metastasis (0.65). CONCLUSION:This study showed a substantial interobserver agreement in the overall interpretation and detecting locoregional and distant involvement with Ga-PSMA PET/CT-MR in PCa patients.
10.1007/s00259-021-05616-5
Prospective comparison of simultaneous [Ga]Ga-PSMA-11 PET/MR versus PET/CT in patients with biochemically recurrent prostate cancer.
Jentjens Sander,Mai Cindy,Ahmadi Bidakhvidi Niloefar,De Coster Liesbeth,Mertens Nathalie,Koole Michel,Everaerts Wouter,Joniau Steven,Oyen Raymond,Van Laere Koen,Goffin Karolien
European radiology
OBJECTIVES:PSMA-PET has become the PET technique of choice to localise the site of biochemically recurrent prostate cancer (PCa). With hybrid PET/MRI, the advantages of MRI are added to molecular characteristic of PET. The aim of this study was to investigate the incremental value of PET/MR versus PET/CT in patients with biochemically recurrent PCa by head-to-head comparison. METHODS:Thirty-four patients with biochemically recurrent PCa were prospectively included. They underwent [Ga]Ga-PSMA-11 PET/CT, followed by simultaneous PET/MR. All PET (PET, PET), CT and MR images were evaluated for number of lesions and location. The number of lesions at specific sites was compared using Wilcoxon-sign-rank test. For PET, the maximum and mean standardised uptake values (SUVs) were calculated for each lesion compared using a two-sided paired t test. RESULTS:PET and PET scans were positive in 19 and 20 patients, detecting 73 and 79 lesions respectively. All lesions detected on PET were also detected on PET. CT and MRI only were positive in 14 and 17 patients, detecting 38 and 50 lesions, respectively, which was significantly lower than PET and PET respectively. Combined interpretation showed more lesions on PET/MR than on PET/CT (88 vs 81). No significant difference in detection of presence of local recurrence nor distant metastases was found. SUV and SUV values were significantly higher on PET than on PET in local recurrence and lymph node metastases. CONCLUSIONS:[Ga]Ga-PSMA-11 PET/MR was able to detect biochemically recurrent PCa at least as accurately as PET/CT for local recurrence, lymph node metastasis and distant metastasis. KEY POINTS:• PSMA PET/MRI detects the location of biochemical recurrence at least as accurately as PET/CT. • Substitution of PET/CT by PET/MRI adds sensitivity in PSMA lesion detection also in the setting of distant recurrence due to both the MR and TOF PET components.
10.1007/s00330-021-08140-0